S227: initial safety data from the phase 3 polar bear trial in elderly or frail patients with diffuse large cell lymphoma, comparing r-pola-mini-chp and r-mini-chop

Background: For patients with diffuse large B-cell lymphoma (DLBCL), overall survival has substantially improved during the last decade. An exception is the group of patients above 80 years of age, a group that also constitutes an increasing proportion of DLBCL patients, primarily due to a demographic shift, with a progressively aging population. Effective and safe treatment for this population is an obvious unmet medical need Aims: In this trial, we aim to evaluate pola-R-miniCHP as first line treatment for elderly/frail patients with DLBCL, compared to the current treatment standard, R-mini-CHOP (NCT04332822). Here, we present data on safety from the first 127 patients in this trial. Methods: Patients with newly diagnosed DLBCL, >80 years, or 75-80 years and frail, according to a simplified Comprehensive Geriatric Assessment, are randomized 1:1 to either the standard treatment for this population, R-miniCHOP, or an experimental regimen, R-pola-miniCHP, both for 6 cycles, where vincristine is substituted by polatuzumab vedotin, 1.8 mg/kg, day 1. In total, 300 patients are planned for enrollment. In this report, the highest grade of adverse event for each category, according to CTCAE v 5, was reported. Reporting of grade 1-2 hematological toxicity was not required according to protocol. Results: Between 01-AUG-2020 and 31-JAN-2023, 127 patients were enrolled, from 37 sites in Sweden, Norway, Denmark, Finland, and Italy, 62 in the standard arm, and 65 in the experimental arm. The median time of follow-up for surviving patients is 11.4 months. 20 patients (16%) were <80 years, and enrolled due to frailty. The majority (69%) were 80-90 years. 15 patients (12%) presented with performance status 3. At the date of data cutoff, 291 cycles of R-mini-CHOP, and 276 cycles of R-pola-mini-CHP were given. There was no difference in terms of grade 3-4 hematological toxicity between the treatment groups. (Figure 1) In terms of infections, there were 9 grade 3 events in both groups (14% in total). Gastrointestinal toxicity > grade 1, particularly diarrhea, was twice as common in the pola group (20 pts, 31%, including one fatal event of intestinal ischemia, not related to treatment), vs in 10 pts (16%) in the R-mini-CHOP group. The was no clear difference in peripheral neuropathy grade 1-2; 8 vs 10 pts in the R-mini-CHOP and R-pola-mini-CHP groups respectively. More grade 1-2 events categorized as “other” were reported in the pola group, but without a clear pattern. In this period, there were 8 deaths reported to be due to adverse events, 6 in the pola arm, of which 2 were considered to be related to polatuzumab vedotin (pneumonia NUD + COVID-19-pneumonia). The two grade 5 events in the standard arm were considered not related to study drug. Summary/Conclusion: In general, both treatment regimens were considered tolerable in this elderly and frail population. The replacement of vincristine with polatuzumab vedotin in R-mini-CHOP was not associated with more grade 3-4 hematological toxicity, risk for infection, or neuropathy, but with a higher frequency of gastrointestinal adverse events. Physicians using this regimen in this elderly population need to be vigilant in the monitoring of these side effects.Keywords: Diffuse large cell lymphoma